The present invention relates to styryl dyes and compositions and to methods for using these dyes and compositions; to porous glass-polymer composites and to methods for using these composites; to methods and compositions for generating singlet oxygen and for killing cells and viruses; and to methods and media for storing and reading data generally and, more particularly, for reading and storing data in three dimensions.
Frequency Upconversion
Frequency upconversion lasing is an important area of research and has become more interesting and promising in recent years. Compared to other coherent frequency upconversion techniques, such as optical harmonic generation or sum frequency mixing based on second- or third-order nonlinear optical processes, the major advantages of upconversion lasing techniques are: i) elimination of phase-matching requirements, ii) feasibility of using semiconductor lasers as pump sources, and iii) capability of adopting waveguide and fiber configurations. To date, two major technical approaches have been used to achieve frequency upconversion lasing: one is based on direct two-photon (or multi-photon) excitation of a gain medium (two-photon pumped); the other is based on sequential stepwise multi-photon excitation (stepwise multi-photon pumped).
The earliest reported two-photon pumped (xe2x80x9cTPPxe2x80x9d) lasing was observed in PbTe crystal at 15xc2x0 K. by Patel et al. Phys. Rev. Lett. 16:971-974 (1966). The pump wavelength was 10.6 xcexcm, and the lasing wavelength was about 6.5 xcexcm. Since then, TPP lasing action has also been observed in a number of other semiconductor crystals (Yoshida et al., Japan. S. Appl. Phys. 14:1987-1993 (1975); Gribkovskii et al., Sov. J. Quantum Electron. 9:1305-1307 (1979); Gao et al., Proc. SPIE-Int. Soc. Opt. Eng. 322:37-43 (1982); and Yang et al., Appl. Phys. Lett. 62:1071-1073 (1993)), but low operating temperature (about 10 to 260xc2x0 K.) requirements limited their usefulness. A few reference papers report room temperature TPP lasing in metal vapor or gas systems (Bloom et al., Appl. Phys. Lett. 24:427-428 (1974); Willenberg et al., Appl. Phys. Lett. 37:133-135 (1980); and Goldston et al., Laser Focus World, 27:27-29 (1991)). In addition, room-temperature upconversion lasing has been successfully achieved in rare-earth-ion doped crystals (Silversmith et al., Appl. Phys. Lett. 51:1977-1979 (1987); MacFarlane et al., Appl. Phys. Lett. 52:1300-1302 (1988); Pollack et al., Appl. Phys. Lett. 54:869-871 (1989); Nguyen et al., Appl. Opt. 28:3553-3555 (1989); and McFarlane Appl. Phys. Lett. 54:2301-2302 (1989)), inorganic glasses (Bennett et al,. Ceram. Trans. 28:321-321 (1992) and Mita et al., Appl. Phys. Lett. 62:802-804 (1993)), and optical fibers (Hanna et al., Opt. Commun. 78:187-194 (1990) and Niccacio et al., IEEE J. Quantum Electron. QE-30:2634-2638 (1994)). These systems essentially involve sequential multiple photon absorption with single photon absorption to intermediate metastable states.
By contrast, there were more reported experimental results of TPP lasing behavior in organic dye solutions using commercial dyes, such as Rhodamine 6G, Rhodamine B, dimethyl POPOP (xe2x80x9cDMPxe2x80x9d), and 1,3,1xe2x80x2,3xe2x80x2-tetramethyl-2,2xe2x80x2-dioxopyrimide-6,6xe2x80x2-carbocyanine hydrogen sulfate (xe2x80x9cPYCxe2x80x9d). (Rapp et al., Phys. Lett. 8:529-531 (1971); Topp et al., Phys. Rev. A3:358-364 (1971); Rubinov et al., Appl. Phys. Lett. 27:358-360 (1975); Prokhorenko et al., Sov. S. Quantum Electron. 11:139-141(1981); Qiu et al., Appl. Phys. B48:115-124 (1989); Zaporozhchenko et al., Sov. J. Quantum Electron. 19:1179-1181 (1989); and Swok et al., Op. Lett. 17:1435-1437 (1992)). However, commercial applications, especially those in recording, printing, display, communication, and the like, require, compact, lightweight, inexpensive, minimal maintenance lasers. In this respect, liquid dye lasers suffer a number of drawbacks, including the toxicity of the solvents used to dissolve the dye, concern over solvent evaporation, flow fluctations in the dye solution, and difficulty of use in terms of size and maintenance. Moreover, most two-photon absorption (xe2x80x9cTPAxe2x80x9d) induced stimulated emissions in dye solutions are cavityless lasing or superradiation (directional ASE). Recently, TPP upconversion stimulated emission was reported by Mukherjee, Appl. Phys. Lett. 62, 3423-3425 (1993) in a 4-dicyanomethylene-2-methyl-6-p-dimethylaminostyryl-4H-pyran (xe2x80x9cDCMxe2x80x9d) doped poly(methyl methacrylate) (xe2x80x9cPMMAxe2x80x9d) channel waveguide configuration.
However, DCM, like most commercial and other known dyes, has a TPA cross-section of from approximately 1xc3x9710xe2x88x9250 cm4-sec to approximately 1xc3x9710xe2x88x9248 cm4-sec, which is insufficient to achieve practical conversion efficiencies. In addition, solid state dye lasers have low damage resistance, which has been attributed to either polymer photodegradation or conversion of the dye to a non-emissive species. In view of the deficiencies in present day solid state dye lasers, dyes having greater TPA cross-sections and solid dye laser systems more resistant to photodegradation are desirable.
Optical Limiting
Optical limiting effects and devices are becoming increasingly important in the areas of nonlinear optics and opto-electronics. In particular, these materials are used in protective eyewear against intense infrared laser radiation exposure, in windows for sensitive detectors, and as stabilizers for laser beams used in optical communications and data processing by reducing beam intensity fluctuation. For optical power limiting applications, the material must have a low absorption of light at low intensity and must show a decrease of transmissivity at high intensities so that, at sufficiently high intensities, transmitted intensity levels off. There are several different mechanisms, such as reverse saturable absorption (xe2x80x9cRSAxe2x80x9d), two-photon absorption (xe2x80x9cTPAxe2x80x9d), nonlinear refraction (including all types of beam-induced refractive index changes), and optically induced scattering, which could lead to optical limiting behavior (Tutt et al., Prog. Quant. Electr. 17:299 (1993)). A number of research studies of optical limiting effects, related to TPA processes in semiconductor materials, have been reported (Walker et al., Appl. Phys. Lett. 48:683 (1986); Chang et al., J. Appl.Phys. 71:1349 (1992); Van Stryland et al., Opt. Eng. 24:613 (1985); and Hutchings et al., J. Opt. Soc. Am. B9:2065 (1992)). However, the two-photon absorption cross section of these materials is quite weak, which limits their applicability in many optical power-limiting situations. The search for new materials having larger TPA cross-sections and stronger optical power-limiting properties in the infrared continues.
Infrared Beam Detection
Since infrared light is not visible to the human eye, focusing, aligning, and adjusting the shape of infrared beams, particularly infrared laser beams, requires the use of a device which permits the user to visualize the beam. Conventional, commercially available infrared detection and indication cards, manufactured by Kodak and Kentek, respectively, typically employ a material which operates on thermal release effect principles, becoming visible when exposed to infrared radiation. Because of the nature of the visible effect, i.e. a color change in the surface layer of the card, the card is opaque and must be viewed from the side from which it is exposed. This is frequently inconvenient and makes beam alignment difficult, if not impossible. Furthermore, the commercially available detection sheets exhibit saturation at intensities lower than those used in most infrared laser applications. Consequently, these cards are of little value in assessing the intensity or intensity profile of the beam to which they are exposed. Moreover these detection cards have undesirably short lifetimes, especially when used to detect intense infrared laser beams, and degrade non-uniformly and unpredictably, making their use unreliable. The nature of the thermal mechanism by which these cards operate results in diffusion of the visible image, especially at the beam""s perimeter. Since beam focus is often assessed and adjusted based on the sharpness of the image created, distortion of the visual image by the detection material is highly undesirable.
Recently, a new infrared detection card, consisting of an inorganic crystal powder dispersed in a plastic substrate cast into a film, has become available. The crystal powder produces visible light by second harmonic generation when exposed to infrared radiation and, consequently, may be observed from either side of the card. Nevertheless, the material is easily saturated, and cannot be used to assess beam intensity or intensity profile due to the scattering or diffusional nature of the dispersed powder. In addition, the low conversion efficiency of non-phase-matched second harmonic generation necessitates the use of large amounts of the crystal to achieve a reasonably visible image. This, when coupled with the high cost of the crystal, makes these infrared detection cards prohibitively expensive for most applications.
For these and other reasons, a needs remain for a transparent infrared detection card which produces an easily discernible image at reasonable cost and for one whose response is not saturated at intensities commonly encountered.
Lasing Media
Lasers (an acronym for light amplification by stimulated emission radiation) are light amplifying devices which produce high intensity pulses of monochromatic light concentrated in a well collimated beam commonly called a laser beam. The laser beam has found wide application in photography, communications, industrial measuring instruments, and the like.
Various materials have been used as lasing media. For example, it is known that stimulated emission can be produced in various organic solutions. The first such solutions were of dyes, as reported by Sorokin et al, IBM Journal, 2:130 (March 1967) (xe2x80x9cSorokinxe2x80x9d), and, since then, devices which have been used to produce such stimulated radiation have commonly been known as xe2x80x9cdye lasersxe2x80x9d. Some materials which fluoresce or scintillate outside the visible spectrum also have been used. A compilation of materials which have served as the active material in dye lasers is provided in Sorokin, in Kagan et al., Laser Focus, 26 (September 1968) (xe2x80x9cKaganxe2x80x9d), and in Hecht, The Laser Guidebook, New York:McGraw Hill, pp. 263-295 (1992) (xe2x80x9cHechtxe2x80x9d).
U.S. patents which describe dye lasers include U.S. Pat. No. 3,541,470 to Lankard et al.; U.S. Pat. No.3,679,995 to Sorokin; U.S. Pat. No. 3,684,979 to Myer et al.; U.S. Pat. No.3,818,371 to Herz et al.; U.S. Pat. No. 4,397,023 to Newman et al.; U.S. Pat. No. 4,603,422 to Fletcher; and references cited therein.
The characteristics of traditional dye lasers which make them attractive are the possibilities of wide spectral range and tunability at low cost. The laser can be operated anywhere in the visible or into the ultraviolet or infrared ranges simply by employing a solution which emits electromagnetic radiation at the desired spectral wavelength.
Traditional dye lasers have not achieved their full potential because of various disadvantages. These include: (1) difficulty in pumping a number of useful materials because of low quantum efficiency or high excited state losses due to singlet-triplet transitions or due to triplet absorptions; (2) low conversion efficiencies, high coupling energy losses, and low repetition rates resulting from thermal effects induced during pumping; and (3) dye circulation problems and other limitations posed by thermal effects.
Several attempts have been made in the prior art to overcome these deficiencies by incorporating a traditional laser dye solution into a solid matrix. For example, Pacheco et al., xe2x80x9cA Solid-State Flash-lamp-Pumped Dye Laser Employing Polymer Hosts,xe2x80x9d Proceedings of the International Conference on Lasers ""87 (1987) (xe2x80x9cPachecoxe2x80x9d) incorporated a laser dye solution into polymer hosts, such as polymethylmethacrylate, polycarbonate, and polystyrene. Polymer hosts, however, are not ideal for dye laser applications because they possess low photostability and low thermal stability.
Avnir, xe2x80x9cThe Nature of the Silica Cage as Reflected by Spectral Changes and Enhanced Photostability of Trapped Rhodamine 6G,xe2x80x9d J. Phys. Chem., 88:5956-5959 (1984) (xe2x80x9cAvnirxe2x80x9d) discloses the incorporation of Rhodamine 6G dye into a sol-gel derived silica matrix by adding the Rhodamine 6G dye to a silica sol prior to gelation. When a dopant compound is mixed into a sol before gelation, however, gradients are inevitably formed in the final product due to the migration of the dopant to the surface of the product during the subsequent aging and drying stages. Reaction byproducts are thus trapped within the matrix. Further, dye lasers prepared according to this method cannot be subjected to high temperature stabilization treatments without risking decomposition of the incorporated dye.
U.S. Pat. No. 4,878,224 to Kuder et al. (xe2x80x9cKuderxe2x80x9d) incorporated a solution of a laser dye and, a solvent into the pores of a porous glass matrix and then sealed the glass matrix to prevent migration of any of the solution components out of the pores. Dye lasers prepared according to this method, however, may be inefficient because solvent selection is highly critical. Not only must the solvent be compatible with the laser dye while in solution, but it must also possess photostability and thermal stability during lasing. Further, it is the solvent taken in combination with the laser dye, rather than the dye alone, which must provide adequate lasing effects.
U.S. Pat. No. 5,222,092 to Hench et al. (xe2x80x9cHenchxe2x80x9d) describes a dye laser comprising a highly porous, consolidated silica sol-gel monolith having incorporated therein a laser dye. The laser dye is introduced into the pores of the matrix in a solvent and the solvent is then removed, thus depositing the dye as an adsorbed layer on the inner surfaces of the pores of the silica sol-gel matrix. Hench further describes sealing the surface of the dye-containing monolith with a polymer by contacting the monolith with an organic polymer solution to prevent migration of the dye out of the pores and to prevent contamination of the pores. However, the material disclosed in Hench possesses voids which contain air which can quench the lasing process. Further, the difference in refractive index between the air and silica sol-gel matrix can result in internal reflections which reduce laser output.
Another approach is based on the methods described in Pope et al., J. Mater. Res., 4:1018 (1989). It involves infusion of a monomer containing the desired lasing dye into a porous sol-gel matrix and then polymerization of the monomer in situ to produce a matrix containing dye dispersed in polymer in the pores of the matrix. The methods are described in Reisfeld et al., SPIE Proc. 1182:230 (1989) (xe2x80x9cReisfeldxe2x80x9d); Gvishi et al., SPIE Proc. 1972:390 (1993) (xe2x80x9cGvishixe2x80x9d); Shamrakov et al., Chem. Phys. Lett. 213:47 (1993) (xe2x80x9cShamrakovxe2x80x9d); He et al., Opt. Comm. 111:82 (1994) (xe2x80x9cHexe2x80x9d); Dunn, xe2x80x9cSol-gel Encapsulated molecules: Optical Probes and Optical Properties,xe2x80x9d in Klein, ed., Sol-Gel Optics: Processing and Applications, Kluwer Academic Publishers, Chapter 14 (1993) (xe2x80x9cDunnxe2x80x9d); Lo et al., Appl. Phys. B, 56:385 (1993) (xe2x80x9cLoxe2x80x9d); and Canva et al., SPIE Proc., 2288:298 (1994) (xe2x80x9cCanvaxe2x80x9d). However, these composites are limited in that the method for their preparation requires that the dye be sufficiently soluble in monomer to produce a material with a dye concentration effective to permit lasing. This limitation is particularly problematic in situations where the lasing proceeds via a two photon absorption mechanism which frequently requires high dye concentrations.
Another deficiency in all of the aforementioned attempts to produce dye-doped matrices for use in lasing applications relates to the desirability of incorporating more than one dye to increase the range of wavelengths at which the laser can emit. Incorporating more than one dye in the solid polymer matrix described in Pacheco, in the sol gel described in Avnir, in the solutions described in Kuder, in the adsorbed layer described in Hench, and in the polymers described in Reisfeld, Gvishi, Shamrakov, He, Dunn, Lo, and Canva inevitably leads to quenching of one of the dyes by the other.
Attempts to incorporate optically-active materials into photostable optically transparent media for use as building blocks for photonic devices has not been limited to lasing dyes. The photonic properties of fullerenes have been a subject of extensive investigation in recent years. Their nonlinear optical properties and optical power limiting behavior have drawn much of the attention (Kafafi et al., SPIE Proceedings on xe2x80x9cFullerenes and Photonicsxe2x80x9d 2284:134 (1994); Justus et al., Opt. Lett. 18:1603 (1993); and Tutt et al., Nature 356:225 (1992)). In addition, luminescence from C60 solutions at room temperature has recently been reported in Kim, J. Am. Chem. Soc. 114:4429 (1992). The past studies have mostly used fullerenes in solution and in a pure solid film form, although fullerene doped polymers have been described in Kost et al., Opt. Lett 18:334 (1993) and Prasad et al., SPIE Proceedings on xe2x80x9cFullerenes and Photonicsxe2x80x9d 2284:148 (1994). However, because of their limited solubility, fullerenes cannot be doped in high concentrations. Furthermore, devices which require a long interaction length (such as optical power limiters) need a high optical quality bulk form. Sol-gel processes offer the ability to prepare high optical quality bulks with a long interaction length. However, due to the limited solubility of fullerenes in solvents used for sol-gel processing, past approaches used fullerene suspensions to prepare films, xerogels (Bentivegna et al., Appl. Phys. Lett. 62:1721 (1993)), and sonogels (McBranch et al, SPIE Proceedings on xe2x80x9cFullerenes and Photonicsxe2x80x9d 2284:15 (1994)). Because the fullerenes are in suspension in the matrix in which they are dispersed, the optical transparency of the composites are compromised, and the long interaction lengths required are not attained.
To overcome the above-described limitations, as well as for other reasons, a need remains for photostable, optically-transparent media which incorporate photoactive materials.
Photodynamic Therapy
A promising new modality for controlling and treating tumors is photodynamic therapy (xe2x80x9cPDTxe2x80x9d). This technique uses a photosensitizer, which localizes at or near the tumor site and, when irradiated in the presence of oxygen, serves to produce cytotoxic materials, such as singlet oxygen (O2(1xcex94g)) from benign precursors (e.g. (O2(3xcexa3gxe2x88x92)). Diamagnetic porphyrins and their derivatives are the photosensitizers of choice for PDT. It has been known for decades that porphyrins, such as hematoporphyrin, localize selectively in rapidly growing tissues including sarcomas and carcinomas. Hematoporphyrin derivative (xe2x80x9cHPDxe2x80x9d) is an incompletely characterized mixture of monomeric and oligomeric porphyrins. The oligomeric species, which are believed to have the best tumor-localizing ability, are marketed under the trade name PHOTOFRI II and are currently undergoing phase III clinical trials for obstructed endobronchial tumors and superficial bladder tumors. The mechanism of action is thought to be the photoproduction of singlet oxygen (O2(1xcex94g)), although involvement of superoxide anion or hydroxyl and/or porphyrin-based radicals cannot be entirely ruled out Promising as HPD is, it and other available photosensitizers (such as the phthalocyanihes and naphthophthalocyanines) suffer from serious disadvantages.
While porphyrin derivatives have high triplet yields and long triplet lifetimes (which allows them to transfer excitation energy efficiently to triplet oxygen), their absorption in the Q-band region parallels that of heme-containing tissues, typically having absorption bands at about 520 nm to about 620 nm. This generally limits the penetration of exciting radiation to depths of 2 to 5 mm. The biologic response is, on average, 2-3 times deeper than the lights direct penetration depth. As a result, the greatest attainable depth of PDT induced cellular changes is up to 15 mm, but, in most cases, it is less then a half this value. Since most of the incident energy used in photo-treatment is dispersed or attenuated by the patients"" tissues before reaching the center of a deep-seated tumor, little of the light is available for singlet oxygen production and therapy at the tumor site.
This has limited the use of PDT to the treatment of tumors at or near the skin surface, such as those involved in bladder carcinomas, skin malignancies, and brain tumors. Clinically, PDT has found clinical use in the treatment of superficial and early tumors of the head and neck, often saving patients from additional surgery. PDT also appears promising as an adjuvant inoperative treatment of recurrent head and neck carcinomas. However, recent statistics from the National Cancer Institute estimate that pancreatic cancer is now the fourth most common cause of cancer death in the United States. One of the factors contributing to the lethality of pancreatic cancer is that the pancreas is deep-seated in the body and is not readily accessible for treatment by PDT.
Attempts to increase the effectiveness of PDT at greater depths by increasing the intensity of the light used to excite the photosensitizers have failed, largely because of the damage that such high intensity light inflicts on heme-containing tissues. On the other hand, attempts to increase the PDT effect by increasing the concentration of porphyrin photosensitizer have been thwarted by the inability of the body to metabolize the photosensitizer rapidly. Significant amounts of the sensitizing porphyrin thus remain in the patient""s body, typically localized in the skin, long after photodynamic tumor treatment has ended, which makes patients photosensitive for weeks following treatment and requires that they stay out of bright light, especially sunlight, for that period. Increasing the dosage of photosensitizer only exacerbates this photosensitivity.
Most efforts to increase the effectiveness of photodynamic treatment of deep-seated or large tumors have focused on developing sensitizers which absorb in the spectral region where living tissues are relatively transparent (i.e. 700-1100 nm).
For example, some phthalocyanines and naphthophthalocyanines absorb in a spectral range in which there is less absorption by heme-containing biological materials. However, they have significantly lower triplet yields, they tend to be quite insoluble in polar protic solvents, and they are difficult to functionalize.
Other compounds, such as porphyrin derivatives having extended xcfx80 networks, purpurins, verdins, chlorophyl-like species, benzoporphyrins, and sulfonated phthalocyanines and napthophthalocyanines have also been tested. Of these, only the napthophthalocyanines absorb efficiently in the desirable  greater than 700 nm spectral region. However, these napthophthalocyanines are difficult to prepare in a chemically pure, water soluble form and have only minimal absorption in regions outside of the regions where heme-containing biological materials absorb.
A third generation of sensitizers, having absorption at longer (650 nm or greater) wavelengths, such as those based on the texaphrin macrocycle described in U.S. Pat. No. 5,439,570 to Sessler et al., have permitted a 30% increase in treatment depths. However, even these sensitizers fail to absorb at wavelengths sufficiently long to permit penetration of the exciting radiation to the depths at which many deep-seated tumors lie.
The photodynamic generation of singlet oxygen has also been exploited in a number of other areas, such as, blood purification. Blood purification has become increasingly important in view of the concern with blood""s role in the transmission of acquired immunodeficiency syndrome (xe2x80x9cAIDSxe2x80x9d). AIDS, first reported in 1981 as occurring among male homosexuals, is a fatal human disease which has now reached pandemic proportions. At present, sexual relations and needle-sharing are the dominant mechanisms for the spread of AIDS. However, cases where infection is transmitted by transfused blood have not been uncommon. Since testing of blood supplies has begun, the number of AIDS infections due to blood transfusions has dropped considerably. However, an absolutely fail-proof means must be developed to insure that all stored blood samples are free of the AIDS virus (and, ideally, other blood-borne pathogens). Serologic tests for HIV-1 are insufficient to detect all infected blood samples, particularly those derived from donors who have contracted the disease but who have not yet produced detectable antibodies.
Since testing procedures cannot, at present, insure that blood is free of the HIV virus, blood purification is an attractive alternative. Any blood purification procedure used to remove AIDS virus or other blood-borne pathogens should operate without introducing undesirable toxins, damaging normal blood components, or inducing the formation of harmful metabolites. This precludes the use of common antiviral systems, such as those based on heating, UV irradiation, or purely chemical means. A promising approach is the photodynamic one alluded to above. Research at the Baylor Research Foundation have shown that HPD and PHOTOFRIN(trademark), in far lower dosages than are required for tumor treatment, act as efficient photosensitizers for the photo-deactivation of cell-free HIV-1, herpes simplex virus (xe2x80x9cHSVxe2x80x9d), hepatitis, and other enveloped viruses. The success of this procedure derives from the fact that these photosensitizers localize selectively at or near the morphologically characteristic and physiologically essential viral membrane (xe2x80x9cenvelopexe2x80x9d) and catalyze the formation of singlet oxygen upon photoirradiation. The singlet oxygen destroys the essential membrane envelope, killing the virus and eliminating infectivity. Photodynamic blood purification procedures, therefore, rely on the use of photosensitizers which localize selectively at viral membranes, just as more classic tumor treatments require photosensiiizers that are absorbed or retained preferentially at tumor sites. Simple enveloped DNA viruses like HSV-1 are good models for testing putative photosensitizers for potential use in killing the far more hazardous HIV-1 retrovirus. This correspondence holds only as far as freely circulating (as opposed to intracellular) viruses are concerned. Complete prophylactic removal of HIV-1 from blood products will require the destructive removal of the virus from within monocytes and T lymphocytes.
The above-described photodynamic blood purification methods suffer from several drawbacks. One of these relates to the porphyrin sensitizer having absorption which is substantially at the same wavelengths as the heme group in hemoglobin, an important constituent in blood. As a result, a portion of the light used to irradiate the photosensitizer is absorbed by the heme. This has two consequences. First, it limits the intensity of the radiation that can be used because the energy absorbed by the heme is dissipated via thermal pathways resulting in localized heating of the hemoglobin protein. At increased intensities, the hemoglobin molecule cannot dissipate the heat to its surroundings fast enough to prevent its thermal denaturation. Second, the absorption of the irradiating light by the heme attenuates the depth to which the light will penetrate. This necessitates that the blood be irradiated in thin vessels or with agitation. Thin vessels have high surface areas which tends to damage the delicate red blood cells. Agitation of blood is often devastating to red blood cells and requires expensive equipment and, even then, cannot be achieved without some loss.
A need, therefore, remains for new photodynamic blood treatment methods and photodynamic therapy protocols.
Data Storage
The need for data storage and processing has been increasing at a high rate. In response to this need, significant advances in memory design have been made. Two major considerations which impact the desirability and utility of various memory devices are cost per bit of information stored and access time. For example, conventional magnetic tape storage costs 10xe2x88x925 ¢/bit and has an access time of 100 seconds. Disk, drum, and core storage have considerably faster access times (300 msec, 10 msec, and 1 xcexcsec, respectively) and considerably higher costs (0.05, 0.01, and 2 ¢/bit, respectively). Semiconductor storage devices offer yet faster access times (100 nsec) but at still higher cost (20 ¢/bit).
Optical data storage systems have access times of 10 nsec and costs which range from 10xe2x88x924 to 10xe2x88x923 ¢/bit. Conventional two-dimensional optical data storage can register information at about 108 bits per square centimeter using visible or infrared wavelengths at the diffraction limit. In view of the increasing need for still less expensive data storage systems with still faster access times, and recognizing that cost and access time is governed in large measure by the density of the stored data, efforts have focused on increasing data storage density.
It has been proposed that by writing and reading data in a three-dimensional format, data storage densities of greater that 1012 bits per cubic centimeter could be achieved. U.S. Pat. Nos. 4,466,080 and 4,471,470 to Swainson et al. (collectively xe2x80x9cSwainsonxe2x80x9d), for example, disclose the use of two intersecting beams of radiation which are matched to selected optical properties of an active medium to form and to detect inhomogeneities. In such a system, a stack of two-dimensional planar bit arrays effectively multiplies data density by the number of planes in the third dimension. In media which are linearly photoactive, the primary difficulty with such a scheme is cross-talk between planes. However, writing with three-dimensional resolution in thick media can be accomplished by using media which are non-linearly photoactive.
Consider, for example, a focused Gaussian beam well below the saturating intensity, incident on a physically thick but optically thin absorbing sample. In the case where the optically active medium is linear, the same amount of energy is absorbed in each plane perpendicular to the axis of the incident beam, irrespective of the distance from the focal plane, because the net flux passing through each plane is approximately the same. Since the photoactivity is of a linear photoactive medium is proportional to absorption, planes above and below the particular plane being addressed are strongly contaminated. Where the photoactive media is quadratically dependent on intensity, however, net excitation per plane falls off with the inverse of the square of the distance from the plane being addressed. Therefore, information can be written in the plane being addressed without significantly contaminating adjacent planes, if the planes are sufficiently spaced.
Several approaches to three-dimensional optical data storage have been investigated. These include: holographic recording on photorefractive media (Poch, Introduction to Photorefractive Nonlinear Optics, New York:John Wiley and Sons (1993) and Gunter et al., eds., Topics in Applied Physics, Vols. 61 and 62 Photorefractive Materials and Their Applications I and II, Berlin:Springer-Verlag, (1989 (Vol. 61) and 1990 (Vol 62))); hole burning (Moerner, ed., Persistent Spectral Hole Burning: Science and Applications Berlin:Springer (1987)), and photon echo (Kim et al., Opt. Lett., 14:423-424 (1989)).
U.S. Pat. No. 5,289,407 to Stickler et al. employs confocal microscopy to write information in a three-dimensional two-photon active liquid acrylate ester blend photopolymer as submicron volume elements of altered index of refraction. Each element is either written (characterized by a changed index of refraction) or unwritten (characterized by an unchanged index of refraction). The pattern of inhomogeneities in the three-dimensional photopolymer are then detected by differential interference contrast or confocal microscopy. The writing speed is slow (on the order of 10 ms), although significant improvement is said to be possible. A more fundamental disadvantage to the method, however, is the need to use a light in the blue region of the visible spectrum to read the stored data Most polymers have reduced transparency in the blue region, and, consequently, the use a blue read light limits the depth at which data can be read.
Two-photon based data storage in polymer systems have also been described in Parthenopoulos et al., xe2x80x9cThree-dimensional Optical Storage Memory,xe2x80x9dScience, 245:843-845 (1989); Parthenopoulos et al., xe2x80x9cTwo-photon Volume Information Storage in Doped Polymer Systems,xe2x80x9d J. Appl. Phys., 68:5814-5818 (1990); Dvornikov et al., Accessing 3D memory Information by Means of Nonlinear Absorption,xe2x80x9d Opt. Comm., 119:341-346 (1995); U.S. Pat. No. 5,268,862 to Rentzepis; and U.S. Pat. No. 5,325,324 to Rentzepis et al. In these systems, two beams (532 nm and 1064 nm) were made to intersect in the bulk of the polymer sample containing a spirobenzopyran dispersed therein. At the point of intersection, the spirobenzopyran undergoes two-photon absorption and transformation to a form which fluoresces when excited by two 1064 nm photons. Each data point could assume one of two states (exposed or unexposed), and, in this manner, data was stored as an three-dimensional array of binary information. The lifetime of the transformed state of the sprirobenzopyran was on the order of minutes at room temperature and on the order of days in dry ice. These lifetimes, though suitable for some applications, do not meet the lifetime requirements of many data storage applications.
For these and other reasons, the need exists for data storage media having the capacity to store information at higher densities.
The present invention relates to a composition which includes a matrix material and a styryl compound dispersed therein. The styryl compound has the formula: 
wherein
D is an electron donating group;
Q is an electron acceptor selected from the group consisting of electron acceptors having the formulae: 
W is an electron accepting group,
R3 is selected from the group consisting of substituted or unsubstituted alkyl or substituted or unsubstituted aryl moieties,
n is an integer from 0 to 4,
A, B, and C are substituents of their rings and are each independently selected from the group consisting of alkyl, alkoxy, hydroxyallyl, sulfoalkyl, carboxyallyl, and hydrogen, and
Y is a counterion.
The present invention also provides a method of detecting infrared radiation. The method comprises placing a styryl compound having the above formula at a location potentially exposed to the infrared radiation and evaluating whether the styryl compound has been exposed to the infrared radiation at the location.
Another aspect of the present invention pertains to a method for reducing intensity of infrared radiation. The method comprises providing a styryl compound having the above formula and passing infrared radiation through the compound.
The present invention also relates to a method for converting infrared radiation to visible radiation. The method includes providing a styryl compound having the above formula and exposing the compound to infrared radiation.
The present invention further relates to a styryl compound having the formula: 
wherein
R1, R2, and R3 are the same or different and are selected from the group consisting of substituted or unsubstituted alkyl or substituted or unsubstituted aryl moieties,
A and B are substituents of their rings and are each independently selected from the group consisting of alkyl, alkoxy, hydroxyalkyl, sulfoalkyl, carboxyalkyl, and hydrogen, and
Y is a counterion.
The styryl compounds and compositions of the present invention have much greater two-photon absorption cross-sections, much stronger upconversion fluorescence emission, and increased stability compared to the organic dyes of the prior art. Moreover, they are inexpensive to make and are readily incorporated into matricies. These and other properties of these compounds make them well-suited for use in two-photon pumped cavity lasing, two-photon pumped up-conversion lasing, optical power limiting, optical power stabilization, optical signal reshaping, and infrared beam detection and indication.
In another aspect, the present invention also relates to a composite comprising a glass having pores. The pores have a pore surface, on which is coated a coating material. The composite further comprises a polymeric material in the pores.
The invention also relates to a process for producing an optically responsive composite. The process comprises providing a glass having pores, which pores have a pore surface coated with an optically responsive coating. A monomeric material is infused into the pores and permitted to polymerize to produce a polymeric material.
The composites of the present invention are of high optical quality and can be large-sized monolithic bulk forms useful in various photonic functions such as lasing, optical power limiting, and non-linear optical response. Because the pores of the glass contain a polymer whose refractive index is closer to the refractive index of the glass than is the refractive index of air, the composites of the present invention exhibit enhanced optical properties. Furthermore, the polymer-filled pores of the composites of the present invention provide a convenient way to prevent migration of the coated material out of the composite as well as to inhibit contamination of the composite with materials which reduce their damage threshold or shorten their lifespan.
The composites are particularly useful to form multiphasic nanostructured composites wherein the phase separation can be on the nanometer scale. By dispersing a second optically responsive material in the polymeric material, a composite having two phases, an interfacial phase comprising the coated material on the pore surface and a polymer phase comprising the dispersed material in the polymer, can be produced. In contrast to composites containing two optically responsive materials mixed in a single phase, the multiphasic nanostructured composites of the present invention retain the optical response characteristic of each material. In terms of applying the present invention to tunable lasers by using two laser dyes which reside in different phases, reduced energy transfer between the dyes results in a composite having a broad tunability range of lasing. Similarly, by using two optical power limiters, each localized in a separate phase of the composite of the present invention, a composite having optical limiting properties over an expanded wavelength and power range can be constructed.
The present invention, in yet another aspect thereof, relates to a method for producing singlet oxygen. A composition which includes a photosensitizer having absorption at a wavelength from about 380 nm to about 760 nm and a dye capable of converting photons having energies of from about 660 to about 1300 nm to photons having energies of from about 380 to about 760 nm is formed. The composition is exposed to light having a wavelength of from about 660 nm to about 1300 nm in the presence of oxygen to produce singlet oxygen.
The present invention also relates to a method of killing cells or viruses. An effective amount of a photosensitizer having absorption at a wavelength from about 380 nm to about 760 nm is provided proximate to the cells or viruses. An effective amount of a dye capable of converting photons having energies of from about 660 to about 1300 nm to photons having an energies of from about 380 to about 760 nm is also provided proximate to the cells or viruses. The dye is then exposed to light having a wavelength of from about 660 to about 1300 nm in the presence of oxygen under conditions effective to produce a cytotoxic effect on the cells or viruses.
In another aspect, the present is directed to a composition which includes a photosensitizer and a dye. The photosensitizer has absorption at a wavelength from about 380 nm to about 760 nm, and the dye is capable of converting photons having energies of from about 660 to about 1300 nm to photons having an energies of from about 380 to about 760 nm. The composition, when exposed to light having a wavelength from about 660 nm to about 1300 nm, produces singlet oxygen.
The methods and compositions of the present invention produce singlet oxygen in masses which are substantially opaque to 380-760 nm light or in situations where a material absorbing 380-760 nm light attenuates the penetration of the 380-760 nm light. These methods and compositions are especially useful when light-induced singlet oxygen generation is desired in biological materials, such as in photodynamic therapy or blood purification protocols.
In yet another aspect , the present invention relates to a method for recording data. A three-dimensional matrix, including a plurality of dye molecules, is provided. A first volume element in the three-dimensional matrix is exposed to actinic radiation for a duration and at an intensity effective to alter detectably a fraction between 0.3 and 0.7 of the dye molecules contained therein. The detectably altered dye molecules are substantially uniformly dispersed in the first volume element.
The present invention also relates to another method for recording data. The method includes providing a three-dimensional matrix including a plurality of dye molecules having the formula: 
wherein D, Q, W, R3, n, A, B, C, and Y are defined as above. The method further includes exposing a first volume element in the three-dimensional matrix to actinic radiation under conditions effective to alter detectably all or a fraction of the dye molecules contained in the first volume element.
In another aspect, the present is directed to a data storage medium. The data storage medium includes a three-dimensional matrix, including a first volume element, and a plurality of dye molecules. A fraction between about 0.3 and about 0.7 of the dye molecules contained in the first volume element are detectably altered, and the detectably altered dye molecules are substantially uniformly dispersed through the first volume element.
The present invention is also directed to a data storage medium which includes a three-dimensional matrix and a plurality of dye molecules substantially uniformly dispersed in the three-dimensional matrix. The dye molecules have the formula: 
wherein D, Q, W, R3, n, A, B, C, and Y are defined as above.
The data storage methods and media of the present invention have approximately 1012 volume elements per square centimeter. Each of the volume elements can store a single bit, digital information of approximately 8 bits, or analog information. Because of its ability to store analog data, such as grayscale value or color density values, the methods and media of the present invention are particularly useful for storing or archiving a series of two-dimensional black and white or color images, such as frames of a movie.